Project Summary Age-related cognitive impairment in racial and ethnic minorities is one of the most important public health issues in the US. The number of adults aged sixty-five and older is expected to double in the next four decades, and the proportion of Hispanic/Latino or non-Hispanic black older adults is also expected to increase rapidly. Hispanics/Latinos and non-Hispanic blacks have a greater risk of cognitive impairment compared to non-Hispanic whites, which could be due to a greater burden of vascular risk factors in these groups. Vascular risk factors may influence macro- and microstructural WM integrity, which may in turn damage gray matter (GM) integrity and lead to cognitive impairment. Though global metrics of WM integrity, such as white matter hyperintensity volume (WMHV), have been associated with cognition extensively, growing evidence suggests that WMHV does not reflect the full extent of WM disease. Recent studies propose that a penumbra of WM damage exists outside of WMH and is better reflected by metrics of microstructural WM integrity. Despite these findings, the relationships between macro- and microstructural WM integrity, GM integrity, and cognition are not well understood in Hispanic/Latino and non-Hispanic black populations with a greater vascular risk factor burden and increased risk for cerebrovascular and cognitive disease as compared to Caucasians. In this proposed study, I will investigate the associations between macro- and microstructural WM integrity, GM integrity, and cognition in the mostly Hispanic/Latino, clinically stroke-free Northern Manhattan Study (NOMAS). The central hypotheses are that MRI-derived, region-specific metrics of macro- and microstructural WM integrity predict cognitive performance, and region-specific metrics of GM integrity partially mediate this association. I also hypothesize that metrics of microstructural WM integrity will associate with cognition independently from and more robustly than metrics of macrostructural WM integrity. Results from this proposed study will provide evidence for potential targets for intervention in these at-risk populations. These study aims support key goals of the National Institute of Neurological Disorders and Stroke (NINDS) Strategic Plan, including: a) investment across the full spectrum of basic, translational, and clinical research; b) promotion of clinical research; and c) establishment of a data-driven process to identify unmet scientific opportunities and public health need within and across neurological disease. The proposed research also addresses the NIH BRAIN Initiative by exploring brain networks through MRI metrics of WM integrity.